大量研究已证明海洋抗菌肽具有抗癌特性。本研究旨在探索罗非鱼 piscidin 4 (TP4)（一种抗菌肽）在人类膀胱癌中抗肿瘤活性的基本分子机制。 TP4通过将细胞周期阻滞在G2/M期，对膀胱癌细胞的增殖表现出显着的抑制作用。此外，TP4 上调 cleaved caspase-3、caspase-9 和 PARP 的表达，导致膀胱癌细胞凋亡途径的激活。 TP4 表现出线粒体活性氧的显着增加，导致线粒体膜电位随后丧失。此外，线粒体氧化磷酸化的抑制导致下游 ATP 产量减少。同时，TP4处理的膀胱癌细胞显示Bax和ERK增加，但SIRT1、PGC-1α和Bcl2减少。 ERK 激活、SIRT1/PGC-1α 轴和 TP4 诱导的细胞凋亡均被 ERK 抑制剂 SCH772984 显着逆转。最后，TP4对肿瘤生长的抑制作用在斑马鱼膀胱癌异种移植模型中得到证实。这些发现表明，TP4 可能通过诱导细胞凋亡、ERK 激活和促进​​ SIRT1 介导的信号通路成为人类膀胱癌的潜在药物。© 2024。作者，获得 Springer Science Business Media, LLC 独家许可，施普林格自然的一部分。

Marine antimicrobial peptides have been demonstrated in numerous studies to possess anti-cancer properties. This research investigation aimed to explore the fundamental molecular mechanisms underlying the antitumor activity of Tilapia piscidin 4 (TP4), an antimicrobial peptide, in human bladder cancer. TP4 exhibited a remarkable inhibitory effect on the proliferation of bladder cancer cells through cell cycle arrest at the G2/M phase. Additionally, TP4 upregulated the expression of cleaved caspase-3, caspase-9, and PARP, leading to the activation of apoptotic pathways in bladder cancer cells. TP4 exhibit a marked rise in mitochondria reactive oxygen species, leading to the subsequent loss of potential for the mitochondrial membrane. Furthermore, the inhibition of mitochondrial oxidative phosphorylation resulted in a decrease in downstream ATP production. Meanwhile, TP4-treated bladder cancer cells showed an increase in Bax and ERK but a decrease in SIRT1, PGC-1α, and Bcl2. ERK activation, SIRT1/PGC-1α-axis, and TP4-induced apoptosis were all significantly reversed by the ERK inhibitor SCH772984. Finally, the inhibitory effect of TP4 on tumor growth has been confirmed in a zebrafish bladder cancer xenotransplantation model. These findings suggest that TP4 may be a potential agents for human bladder cancer through apoptosis induction, ERK activation, and the promotion of SIRT1-mediated signaling pathways.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.